The experiments outlined in this proposal focus on mechanisms regulating the activity of rat brain dopamine-beta-hydroxylase, the enzyme responsible for converting dopamine to norepinephrine in catecholamine containing neurons. Making use of an in vivo method for estimating brain enzyme activity we will first study the effects of a variety of environmental stimuli (including cold stress, electric footshock, electroconvulsive shock, immobilization, and social stress) on dopamine-beta-hydroxylase. We will be particularly interested in the potential regulatory mechanisms controlling in vivo enzyme activity in the face of these stresses. By comparing brain enzyme activity in vivo with that estimated by standard in vitro techniques we will be able to differentiate between altered activity of existing enzyme protein and adaptive changes in enzyme protein level. The stimulus specificity and temporal patterns of altered dopamine-beta-hydroxylase activity will be explored. The second phase of the proposed research will be a natural extension of the above studies. We will investigate how an animal's response to a given stimulus modifies the effect of that stimulus on mechanisms controlling brain dopamine-beta-hydroxylase activity and/or enzyme protein. The latter phase of the proposed research, then, asks how brain dopamine-beta-hydroxylase is related to behavioral function. One important aspect of this proposal rests in documentation of potential alterations which could occur in other species, including man, where brain catecholamine metabolism is thought to be intimately related to behavioral function. With respect to dopamine-beta-hydroxylase specifically, recent reports indicate that schizophrenics may be deficient in this enzyme; research contained in this proposal may reveal new insights into mechanisms responsible for this brain enzyme deficit in mental illness.